The effects of the alpha2-adrenergic agonist, dexmedetomidine, in the spinal nerve ligation model of neuropathic pain in rats.
Peripheral nerve injury may lead to neuropathic pain. Alpha2-adrenergic agonists acting in the descending inhibitory tracts of the spinal cord are effective in acute nociceptive, inflammatory, and, possibly, neuropathic pain. We studied the prevention and treatment of neuropathy with the selective alpha2-adrenergic agonist dexmedetomidine in male Sprague-Dawley rats with unilateral peripheral mononeuropathy resulting from tight ligation of the L5 and L6 spinal nerves. Rats with ligation injury developed mechanical and cold allodynia, but not heat hyperalgesia. Dexmedetomidine (120 microg/kg subcutaneously [S.C.] 30 min before the injury) did not attenuate mechanical or cold allodynia. Dexmedetomidine infusions (60 microg/d for 7 days after the injury, or 30 microg/d for 7 days started 14 days after the injury) did not attenuate mechanical or cold allodynia in the ipsilateral paw, but they increased mechanical allodynia during the latter treatment in the paw contralateral to the injury. Atipamezole (1 mg/kg S.C.) induced mechanical and cold allodynia in rats that had not developed allodynia in 14 days after the injury. In conclusion, although alpha2-adrenergic mechanisms are recognized as important in the development of neuropathic pain-like symptoms in this animal model, we found no favorable effect from systemic treatment with dexmedetomidine at tolerable doses.


CONCLUSIONS
We studied the prevention and treatment of nerve injury-induced pain with the alpha2-adrenergic agonist dexmedetomidine in an animal model. At tolerable doses, systemic dexmedetomidine neither prevented nor attenuated neuropathic pain behavior.
Kontinen
V K
VK
Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Helsinki, Finland. vesa.kontinen@helsinki.fi
Paananen
S
S
Kalso
E
E
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D003080:Cold Temperature; D005121:Extremities / Q000294:innervation; D006358:Hot Temperature; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D008954:Models, Biological; D010146:Pain / Q000503:physiopathology*; D059348:Peripheral Nerve Injuries; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D020926:Medetomidine